Hallucinogen Persisting Perception Disorder After Ibogaine Treatment for Opioid Dependence

Belgers and colleagues report a single-patient case that arose in the context of a Phase II clinical trial of ibogaine for patients with opioid use disorder. The trial focused on cardiac safety; the extracted text does not provide full trial inclusion/exclusion criteria, randomisation, or broader recruitment details beyond this participant’s enrolment. The patient was a 31‑year‑old man with a long history of heroin dependence who had been receiving methadone maintenance (80 mg daily) but continued to use heroin. Screening identified attention‑deficit/hyperactivity disorder but no other current psychiatric diagnoses according to the Mini‑International Neuropsychiatric Interview as reported in the extraction. Procedurally, methadone was replaced with morphine sulfate (reported as 6 × 20 mg/day in the extracted text) because both methadone and ibogaine can prolong QT interval. The participant received a single oral dose of purified ibogaine hydrochloride at 10 mg/kg (700 mg). Monitoring included psychiatric and physical examinations, laboratory testing, and electrocardiographic (ECG) surveillance for QTc changes; objective and subjective opioid withdrawal scales were used to monitor withdrawal. No formal psychometric scales for perceptual symptoms are described in the extracted text. When persisting distressing perceptual symptoms developed, a non‑pharmacological intervention was applied: Eye Movement Desensitization and Reprocessing (EMDR) therapy was initiated 20 days after ibogaine administration to target the distressing memory representations. Pharmacological management of opioid craving and substitution is described later in the course (the extracted text reports initiation of buprenorphine/naloxone 16/4 mg daily after one week to manage craving), but no systematic medication trial for the perceptual symptoms is reported prior to EMDR.

Initial acute effects and safety findings are described in detail for the single participant. During the first five hours after ibogaine ingestion the patient experienced eyes‑closed visual hallucinations and perceptual distortions (oneirogenic phenomena), while remaining awake and oriented to person and place but not time. These acute experiences resolved fully by five hours post‑dose. Objective physiological changes included QTc prolongation on ECG from a baseline of 420 milliseconds to a peak of 516 milliseconds, an accompanying mild fall in heart rate (88 to 69 beats per minute) and blood pressure (135/69 to 113/62 mm Hg), and a mild ataxia (score 10/40 on the Scale for the Assessment and Rating of Ataxia). All physical symptoms reportedly resolved within 24 hours. A clinically significant recurrence of visual imagery occurred 48 hours after ibogaine administration. These recurrent experiences were intrusive, comprised complex scenes previously seen during the oneirogenic episode (for example, images of being laid in a basket as an infant and of discovering a deceased friend), and provoked intense emotions of rejection, shame and guilt. The patient remained well oriented and showed no cognitive impairment, delirium, depression, anxiety, or other psychiatric signs in the days following recurrence as presented in the extracted text. The study team interpreted these symptoms as hallucinogen persisting perception disorder (HPPD) meeting DSM‑5 criteria for clinically significant distress. The perceptual symptoms persisted for weeks. Management included supportive care in the clinical setting and, one week after the recurrence, initiation of buprenorphine/naloxone 16/4 mg daily to address opioid craving. Because the images were highly distressing, EMDR therapy was started 20 days after ibogaine administration; after a single EMDR session the patient reported substantial symptom relief and the images gradually faded over the subsequent 14 days. Despite reduction of HPPD‑related distress, opioid craving remained severe and the patient relapsed to heroin use two weeks after EMDR treatment. Subsequent treatment efforts did not regain control over heroin use according to the extracted text.

Belgers and colleagues highlight that this is the first reported case of HPPD following ibogaine administration. They note that while acute psychotropic effects of ibogaine are well described, psychiatric sequelae in the literature have been limited to a small number of mania and psychosis cases, and no prior ibogaine‑associated HPPD reports were identified in the sources the authors cite. The investigators considered alternative diagnoses, including delirium from opioid withdrawal, precipitation of preexisting psychiatric illness (for example post‑traumatic stress disorder or primary psychotic disorder), or prolonged oneirogenic intoxication. They argue these are less likely given the timing (recurrence 48 hours after dosing), the absence of prior similar symptoms, and the lack of concurrent cognitive disturbance, disorientation or other psychiatric signs in the period of persistence. Pharmacokinetic considerations are discussed: ibogaine has a reported plasma half‑life of 4–7 hours, making direct pharmacologic action at 48 hours improbable, whereas its metabolite nor‑ibogaine has a much longer half‑life and remains active beyond 48 hours. The authors nevertheless consider a causal role for nor‑ibogaine less likely because QTc prolongation—attributed in part to nor‑ibogaine—had normalised within 24 hours while the visual phenomena persisted for nearly five weeks. In placing the case in context, the paper summarises that HPPD has been described after other serotonergic and recreational drugs (LSD, psilocybin, cannabis, MDMA/ecstasy) and cites the DSM‑5 estimate of a 4.2% incidence among people who use drugs, while emphasising that the phenomenology of HPPD varies from complex flashback scenes to simpler visual distortions such as visual snow or afterimages. The pathophysiology is noted to be poorly understood; prior reviews have not produced a unified model and various hypotheses implicate overactivation of visual neural pathways and interaction with anxiety or arousal systems. With respect to treatment, the authors state that pharmacological options reported in case literature include benzodiazepines, antipsychotics, serotonergic agents, adrenergic agents and opioid antagonists, but none have been systematically evaluated. They report successful reduction of HPPD‑related distress with EMDR in this case and explain their rationale: high arousal associated with reliving of the images, prior reports of EMDR diminishing craving in addiction, and a desire to limit additional medications during a Phase II safety trial. The authors emphasise that EMDR appeared to reduce the vividness and emotional distress of the visual memories but did not reduce opioid craving and did not prevent relapse. They conclude by underscoring the need for psychiatric monitoring in addition to physical monitoring when using ibogaine and suggest that EMDR for HPPD‑related distress merits further study.